With the Liga title race entering the home straight, it is leaders Real who have the advantage and victory on Sunday at the Bernabeu would move Carlo Ancelotti's side seven points clear of their bitter rivals.
Such a gap would prove almost impossible for Barca to overturn as there are just nine league games left after this weekend's crunch clash.
And defender Jordi Alba concedes that the visitors simply must win if they are to retain realistic hopes of holding on to the Spanish top-flight crown.
"It's vital to win away to Madrid," Alba told Barca's official website. "We have to win in order to keep our title hopes alive.
"We're going to Madrid with the intention of winning the game. We know it will be difficult, but we want to play a good game and win."
It is a fixture that comes soaked in history and a host of stellar names have contributed to its rich tapestry, not least of all Lionel Messi and Cristiano Ronaldo.
Two prolific forwards with a penchant for delivering on the big occasion, the duo have netted 30 Clasico goals between them and Messi will become the fixture's all-time leading scorer if he can take his tally to 19 this weekend.
That would eclipse the exploits of the legendary Alfredo Di Stefano, who is one of just three players to have scored more goals for Real than Ronaldo.
The Portuguese has racked up a phenomenal 242 goals since moving to the Bernabeu in 2009, ensuring his place among the pantheon of footballing greats.
Ronaldo was silenced by Gerardo Martino's men in October's meeting at Camp Nou, though, as the home side ran out 2-1 winners.
It was another global superstar who took centre stage that day, Neymar grabbing his first Clasico strike to put Barca ahead, with Alexis Sanchez doubling that lead before Jese Rodriguez's late consolation strike.
That result moved Martino's men six points clear of Real, but the side from Madrid have not lost in any competition since then - a run stretching 31 matches.
It marks a significant turnaround from last season, when Barca stormed to the title with 100 points, leaving Real trailing 15 behind.
And this term has seen the emergence of a third genuine championship contender, with Atletico Madrid, who will face Barca in the UEFA Champions League quarter-finals, adding another dimension to a fascinating title battle.
Real, drawn to face Borussia Dortmund in the same competition, will be without Jese, whose season was this week ended by a knee injury, but fellow forward Karim Benzema, who missed Tuesday's Champions League win over Schalke after limping off early in the 1-0 league triumph at Malaga, should return.
Barca may opt to recall Gerard Pique after the defender was left out of last Sunday's 7-0 win over Osasuna as a yellow card in the match would have earned him a suspension.
Jonathan dos Santos (knee) and Isaac Cuenca (hamstring) remain sidelined.
